1. Field of Invention
The present invention relates to the treatment and prevention of inflammatory and hyperproliferative diseases of body cavities, more particularly to the treatment and prevention of diseases of the nasal cavity by phototherapeutical methods.
2. Description of Related Art
The treatment and prevention of inflammatory diseases of the nasal mucous membrane and paranasal sinuses is an unsolved problem. These diseases include allergic rhinitis, commonly referred to as hay fever, vasomotor rhinitis, non-allergic eosinophilic rhinitis, chronic sinusitis, which is the inflammation of the paranasal sinuses, and nasal polyps.
Rhinitis is an inflammatory disorder of the nasal mucous membrane, which is characterized by nasal itch, sneeze, nose running, nasal blockage, and rarely by loss of smelling. The inflammation of the nasal mucous membrane is frequently associated with the inflammation of the paranasal sinuses (rhinosinusitis, chronic sinusitis). As a consequence of the frequent and persistent inflammation of the mucous membrane hyperproliferative lesions, or so-called polyps develop on the mucous membrane.
One characteristic disease is the allergic rhinitis, commonly referred to as hay fever. The allergic rhinitis is the most frequent allergic disease affecting 10–20% of the population. The number of patients with allergic rhinitis, especially in the well developed industrial countries increased very rapidly in the last few years. Because of the high number of patients the direct and indirect costs of this disease are great.
Although hay fever is not a very severe disease, its unpleasant symptoms worsen the quality of life considerably. Hay fever is frequently associated with allergic conjunctivitis and sometimes with general symptoms. The symptoms last only for a few months in some patients (seasonal rhinitis), while in others they last the whole year (perennial rhinitis).
The symptoms of the allergic diseases develop as follows. An allergen enters the body and induces the production of a specific IgE, which binds to specific receptors on the surface of mast cells. After subsequent exposure the allergen crosslinks the IgE receptors, resulting in mediator release from the mast cells. These mediators are responsible for the development of the symptoms in patient.
As a result of this activation histamine and other preformed mediators are released from the mast cells. In the mast cells new inflammatory mediators are produced attracting further inflammatory cells into the mucous membrane (Howarth PH, Salagean M, Dokic D: Allergic rhinitis: not purely a histamine-related disease. Allergy 55: 7–16, 2000).
At present there is no known treatment for rhinitis. The increased number of inflammatory cells in the nasal mucous membrane release mediators, which are responsible for the clinical symptoms. Often antihistamines are used locally or systemically for the blocking of the released mediators. Sodium cromoglycate is available for the inhibition of the release of mediators. Finally, corticosteroids are used locally or systemically for the blocking of the synthesis of new mediators. In special cases a desensitizing therapy might be used. The pathogenesis of the development of the clinical symptoms is already well known. However, the presently available drugs often do not eliminate the symptoms. Therefore, every new method for the treatment of this disease has a great medical significance.
A further characteristic disease is vasomotor rhinitis. Vasomotor rhinitis is an inflammatory disorder of the nasal mucous membrane with unknown origin. The clinical symptoms are largely similar to that of allergic rhinitis: permanent nasal blockage, nasal itch, sneeze, nose running, and rarely loss of smelling. Mastocyte-activating mediators cause the symptoms. These are released from the nerve endings of the nasal mucous membrane upon irritation.
A further characteristic disease is the nonallergic eosinophilic rhinitis. This disease is characterized by the high number of eosinophils in the nasal secretions and by the lack of an allergic origin. The disease is frequently associated with the development of nasal polyps, the hyperproliferative condition of the nasal mucous membrane. The clinical symptoms are the same as in allergic rhinitis.
Additional diseases are rhinosinusitis and sinusitis. The inflammation of the paranasal sinuses is frequently associated with the inflammatory condition of the nasal mucous membrane (nasosinusitis). The isolated inflammation of the paranasal sinuses is also a frequent disease (sinusitis). This disease has often an allergic origin, although its exact cause remains unknown. There is no well-tested treatment, thus usually the same therapy is used as for rhinitis.
Ultraviolet light has been used for more than twenty years for the treatment of allergic and auto-immune skin diseases. In various treatments and procedures ultraviolet-B light (280 nm–320 nm) and ultraviolet-A light (320 mn–400 nm) is used typically. The ultraviolet light inhibits the antigen-induced cellular immune response and is able to induce tolerance (Streilein J W, Bergstresser P R: Genetic basis of ultraviolet-B on contact hypersensitivity. Immunogenetics 27: 252–258, 1988).
The ultraviolet light suppresses the immune reaction by inhibiting the antigen presentation and by inducing T-cell apoptosis. Irradiation of the skin with ultraviolet-B light or ultraviolet-A light on an area previously photosensitized by psoralen is known to inhibit the immunological processes in the skin. For the treatment of skin diseases there are a number of phototherapeutical devices available.
These phototherapeutical devices include ultraviolet light sources. These light sources might be classified based on, for example, their operational principle, output energy or power, mode of operation (impulse or continuous), and whether they are emitting monochromatic or multiwavelength light.
In early treatments broad band ultraviolet B (BB-UVB) light sources were used. In recent years more efficient narrow band ultraviolet B (NB-UVB) light sources became popular (Degitz K, Messer G, Plewig G, Röcken M: Schmalspektrum-UVB 311 nm versus Breitspektrum-UVB. Neue Entwicklungen in der Phototherapie. Hautarzt 49: 795–806, 1998).
Our previous investigations of psoriatic patients indicated that the 308 nm xenon chloride excimer laser is more effective for phototherapeutical treatments than the NB-UVB light sources (Bónis B, Kemény L, Dobozy A, Bor Zs, Szabó G, Ignácz F: 308 nm UVB excimer laser for psoriasis. Lancet 35: 1522, 1997; Kemény L, Bónis B, Dobozy A, Bor Z, Szabo G, Ignacz F: 308-nm excimer laser therapy for psoriasis. Arch Dermatol. 137: 95–96, 2001).
Phototherapeutical treatments improved significantly with the appearance of ultraviolet light delivering optical systems. Such an ultraviolet light delivering phototherapeutical system with fiber optic is used in the Saalmann Cup instrument, in which the concentrated ultraviolet light is coupled into a fiber optic cable. Therefore, it is suitable for the treatment of smaller lesions of the skin or mucous membrane (Taube K M, Fiedler H: Hochkonzentrierte UV Bestrahlung kleiner Hautbezirke mit einem neuen Punktstrahler. Grundlagen und klinische Ergebnisse. Deutsche Dermatologe, 10: 1453, 1992).
However, the Saalmann Cup can not be introduced into smaller body cavities because of its large contact area and because of the thickness of the used fiber optic cable. This device can be used in body cavities where the distal end of the fiber optic cable and the area to be treated can be visually controlled, such as the oral cavity. For this reason, this device is unsuitable for the treatment of body areas, which cannot be visually controlled, such as the nasal and paranasal mucous membrane, the gastrointestinal, and the urogenital mucous membrane.
Although ultraviolet light has been used for the treatment of hyperproliferative and inflammatory skin diseases for many years, it has not been used for the treatment of common, immunologically mediated disorders of the nasal mucous membrane. Neuman and Finkelstein used narrow-band, low energy, red-light phototherapy for the treatment of the nasal mucous membrane and they found it effective for perennial allergic rhinitis and for nasal polyposis (Neuman I, Finkelstein Y Narrow-band red light phototherapy in perennial allergic rhinitis and nasal polyposis. Ann Allergy Asthma Immunol 78: 399–406, 1997).
There are a number of ultraviolet light delivery systems, which use lasers. For example, the light of the 308 nm xenon chloride excimer laser can be guided by fiber optic cable for the cleaning of root canals by ablation (Folwaczny M, Mehl A, Haffner C, Hickel R: Substance removal on teeth with and without calculus using 308 nm XeCl excimer laser radiation. An in vitro investigation. J. Clin. Periodontol 26: 306–12, 1999). The 308 nm xenon chloride excimer laser is also suitable to treat artherosclerosis by treating the blood vessel walls (U.S. Pat. No. 4,686,979), or to enhance the cardiac oxygenization with transmyocardial laser revascularisation (U.S. Pat. No. 5,976,124), or inhibiting neovascularisation during angioplasty by destroying myocardial cells (U.S. Pat. No. 5,053,033).
These systems share the common feature that the high-energy ultraviolet light at the end of the light delivering system is focused on small areas of only a few hundred microns in diameter. This intense ultraviolet light carries out its effect by breaking some of the chemical bonds. However, the intense ultraviolet light damages the tissues with its ablative effect.
It is also known that larger skin lesions can be treated by using a number of small fiber optic cables (U.S. Pat. No. 6,071,302; WO9607451, Asawanonda P, Anderson R R, Chang Y, Taylor C R: 308-nm excimer laser for the treatment of psoriasis: a dose-response study. Arch Dermatol 136: 619–24, 2000).
Phototherapeutical systems attached to endoscopes are also used for the photodynamic treatment of tumors, such as bladder carcinoma or bronchial cancer. However, in these instruments no ultraviolet light is used, and they have special distal ends for tumor treatment (U.S. Pat. Nos. 4,313,431; 4,612,938; 4,676,231; 4,998,930; 5,146,917).
At present, the phototherapeutical systems delivering ultraviolet light consist of a hand piece specifically shaped to a special problem. As such, they are either unsuitable or inconvenient for the treatment of small body cavities such as the nasal cavity with visual control.
Finally, only the light of small concentrated ultraviolet light sources can be coupled with good efficiency into thin optical fiber cables, which have a diameter of a few tenth of millimeter. Ultraviolet lasers are suitable for this purpose, but they are expensive.